EFFECTS OF RECOMBINANT HUMAN TRANSFORMING GROWTH FACTOR-BETA(1) OR AND INTERLEUKIN-6 ON GROWTH-INHIBITION AND PROTOONCOGENE C-MYC EXPRESSION IN HUMAN LEUKEMIA-CELLS/

Objective To examine the effect of recombinant human transforming grow th factor-beta 1 (rhTGF-beta 1) alone or recombinant human interleukin 6 (rhIL-6) alone or in combination on proliferation inhibition of the human leukaemia cell line. Methods In the present study, using the hu man monoblastic cell line (U-937) and human promyelocytic cell line (H L60) as an in vitro model, we analyzed the effect of two cytokins on p roliferation inhibition with rate of H-3-TdR incorporation, the cellul ar content of DNA, DNA indices, the cell cycle and the expression of c -myc mRNA. Results With administration of rhTGF-beta(1) and rhIL-6, U- 937 cell growth was inhibited and the rate of H-3-TdR incorporation in hibition was increased. There was a decrease in the cellular content o f DNA and DNA indices. And no change in the cell cycle was observed af ter administration of rhTGF-beta(1) or rhIL-6. However, there was an i ncrease in G(0)/G(1) phase cells and a decrease in G(2)M+S phase cells after administration of combination of rhTGF-beta 1 and rhIL-6. It wa s also found that rhIL-6 could inhibit proliferative responses of HL60 , cells, meanwhile the inhibition could be enhanced by rhTGF-beta(1). The rate of 3H-TdR incorporation inhibition rose up to 39. 89%, and DN A index fell to 1. 00 following induction by rhIL-6 plus rhTGF-beta(1) . Furthermore, G(0)/G(1) phase cells increased while G(2)M+S cells dec reased. Conclusions These results suggest that combination of rhTGF-PI and rhIL-6 acted in synergy to inhibit proliferation of both U-937 an d HL60 cell lines. Molecular hybridization test show that rhTGF-PI alo ne, rhIL-6 alone or rhTGF-beta(1) and rhIL-6 in combination can inhibi t U-937 and HL60 cells expression of c-myc mRNA in a time and dose dep endent manner. rhTGF-beta 1 and rhIL-6 in combination synergistically inhibited c-myc expression, which may be one of the machanisms for the actions of the two cytokines.